Age affects antibody levels and anthelmintic treatment efficacy in a wild rodent

Abstract

The role of the host immune system in determining parasite burdens and mediating within-host parasite interactions has traditionally been studied in highly controlled laboratory conditions. This does, however, not reflect the diversity of individuals living in nature, which is often characterised by significant variation in host demography, such as host age, sex, and infection history. Whilst studies using wild hosts and parasites are beginning to give insights into the complex relationships between immunity, parasites and host demography, the cause-and-effect relationships often remain unknown due to a lack of high resolution, longitudinal data. We investigated the infection dynamics of two interacting gastrointestinal parasites of wild wood mice (Apodemus sylvaticus), the nematode Heligmosomoides polygyrus and the coccidian Eimeria hungaryensis, in order to assess the links between infection, coinfection, and the immunological dynamics of two antibodies (IgG1 and IgA). In an anthelmintic treatment experiment, mice were given a single oral dose of an anthelmintic treatment, or control dose, and then subsequently followed longitudinally over a period of 7–15 days to measure parasite burdens and antibody levels. Anthelmintic treatment successfully reduced burdens of H. polygyrus, but had no significant impact on E. hungaryensis. Treatment efficacy was driven by host age, with adult mice showing stronger reductions in burdens compared to younger mice. We also found that the relationship between H. polygyrus-specific IgG1 and nematode burden changed from positive in young mice to negative in adult mice. Our results highlight that a key host demographic factor like age could account for large parts of the variation in nematode burden and nematode-specific antibody levels observed in a naturally infected host population, possibly due to different immune responses in young vs. old animals. Given the variable success in community-wide de-worming programmes in animals and humans, accounting for the age-structure of a population could increase overall efficacy.

Variation in Local and Systemic Pro-Inflammatory Immune Markers of Wild Wood Mice after Anthelmintic Treatment

“…2B), with OPGs being four-fold higher than control mice, which is consistent with our previous results (Knowles et al. 2013; Clerc et al. 2019a, 2019b).…”

“…5); lower production of local TNF-α was found in older, treated mice, while there was no effect of age on local TNF-α production in control mice. These interactions between host characteristics and anthelmintic treatment suggest that hosts are impacted differently by the reduction in H. polygyrus burden depending on their age or sex (see Clerc et al. 2019a).…”

“…1989; Wahid and Behnke 1993; Babayan et al. 2018a; Clerc et al. 2019a), or an equal volume of water as a control.…”

“…Mice were sacrificed ∼2-weeks after initial capture and treatment (anthelmintic or control), as previous work with wood mice has shown that anthelmintic drug treatments reduce H. polygyrus burdens for only about 10–16 days (Knowles et al. 2013; Clerc et al. 2019a).…”

Supplemented nutrition increases immunity and drug efficacy in a natural host-helminth system

“…Ivermectin and Pyrantel pamoate are broad-spectrum anthelminthics which target adult and larval stages (Ivermerctin) and adult stages (Pyrantel) of H. polygyrus in both laboratory and wild mice [7][8][9]. Previous work in wild A. sylvaticus found that the combination of Ivermectin and Pyrantel at 9.4mg/kg and 100 mg/kg, respectively, efficiently cleared H. polygyrus infection for ~14 days [10].…”